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Psychological trauma exposure and posttraumatic stress disorder (PTSD) have been associated with advanced epigenetic age. However, whether epigenetic aging measured at the time of trauma predicts the subsequent development of PTSD outcomes is unknown. Moreover, the neural substrates underlying posttraumatic outcomes associated with epigenetic aging are unclear.
We examined a multi-ancestry cohort of women and men (n = 289) who presented to the emergency department (ED) after trauma. Blood DNA was collected at ED presentation, and EPIC DNA methylation arrays were used to assess four widely used metrics of epigenetic aging (HorvathAge, HannumAge, PhenoAge, and GrimAge). PTSD symptoms were evaluated longitudinally at the time of ED presentation and over the ensuing 6 months. Structural and functional neuroimaging was performed 2 weeks after trauma.
After covariate adjustment and correction for multiple comparisons, advanced ED GrimAge predicted increased risk for 6-month probable PTSD diagnosis. Secondary analyses suggested that the prediction of PTSD by GrimAge was driven by worse trajectories for intrusive memories and nightmares. Advanced ED GrimAge was also associated with reduced volume of the whole amygdala and specific amygdala subregions, including the cortico-amygdaloid transition and the cortical and accessory basal nuclei.
Our findings shed new light on the relation between biological aging and trauma-related phenotypes, suggesting that GrimAge measured at the time of trauma predicts PTSD trajectories and is associated with relevant brain alterations. Furthering these findings has the potential to enhance early prevention and treatment of posttraumatic psychiatric sequelae.
Dietary fibre modulates gastrointestinal (GI) health and function, providing laxation, shifting microbiota, and altering bile acid (BA) metabolism. Fruit juice production removes the polyphenol- and fibre-rich pomace fraction. The effects of orange and apple pomaces on GI outcomes were investigated in healthy, free-living adults. Healthy adults were enrolled in two double-blinded, crossover trials, being randomised by baseline bowel movement (BM) frequency. In the first trial, subjects (n 91) received orange juice (OJ, 0 g fibre/d) or OJ + orange pomace (OJ + P, 10 g fibre/d) for 4 weeks, separated by a 3-week washout. Similarly, in the second trial, subjects (n 90) received apple juice (AJ, 0 g fibre/d) or AJ + apple pomace (AJ + P, 10 g fibre/d). Bowel habit diaries, GI tolerance surveys and 3-d diet records were collected throughout. Fresh faecal samples were collected from a participant subset for microbiota and BA analyses in each study. Neither pomace interventions influenced BM frequency. At Week 4, OJ + P tended to increase (P = 0·066) GI symptom occurrence compared with OJ, while AJ + P tended (P = 0·089) to increase flatulence compared with AJ. Faecalibacterium (P = 0·038) and Negativibacillus (P = 0·043) were differentially abundant between pre- and post-interventions in the apple trial but were no longer significant after false discovery rate (FDR) correction. Baseline fibre intake was independently associated with several microbial genera in both trials. Orange or apple pomace supplementation was insufficient to elicit changes in bowel habits, microbiota diversity or BA of free-living adults with healthy baseline BM. Future studies should consider baseline BM frequency and habitual fibre intake.
Although pulmonary artery banding remains a useful palliation in bi-ventricular shunting lesions, single-stage repair holds several advantages. We investigate outcomes of the former approach in high-risk patients.
Retrospective cohort study including all pulmonary artery banding procedures over 9 years, excluding single ventricle physiology and left ventricular training.
Banding was performed in 125 patients at a median age of 41 days (2–294) and weight of 3.4 kg (1.8–7.32). Staged repair was undertaken for significant co-morbidity in 81 (64.8%) and anatomical complexity in 44 (35.2%). The median hospital stay was 14 days (interquartile range 8–33.5) and 14 patients (11.2%) required anatomical repair before discharge. Nine patients died during the initial admission (hospital mortality 7.2 %) and five following discharge (inter-stage mortality 4.8%). Of 105 banded patients who survived, 19 (18.1%) needed inter-stage re-admission and 18 (14.4%) required unplanned re-intervention. Full repair was performed in 93 (74.4%) at a median age of 13 months (3.1–49.9) and weight of 8.5 kg (3.08–16.8). Prior banding, 54% were below the 0.4th weight centile, but only 28% remained so at repair. Post-repair, 5/93 (5.4%) developed heart block requiring permanent pacemaker, and 11/93 (11.8%) required unplanned re-intervention. The post-repair mortality (including repairs during the initial admission) was 6/93 (6.5%), with overall mortality of the staged approach 13.6% (17/125).
In a cohort with a high incidence of co-morbidity, pulmonary artery banding is associated with a significant risk of re-intervention and mortality. Weight gain improves after banding, but heart block, re-intervention, and mortality remain frequent following repair.
The prevalence of allergies in children has grown in last few decades. Allergies are very often associated with physical, mental, and emotional problems that could be detected through child’s behaviour and feelings.
to describe and compare children’s behaviour (internalizing and externalizing) across a sample of children aged 6–11 years with and without allergic diseases.
This was a cross-sectional observational case-control study. A survey to 366 families (194 allergic cases and 172 controls), including a child behaviour checklist (CBCL) and a socio-demographic questionnaire with questions related to family, school education, health conditions and allergy symptoms, was administered.
Children with a diagnosis of allergy showed higher scores in the overall CBCL score (standardised mean differences [SMD]= 0.47; confidence intervals [CI]: 0.26–0.68) and in the internalizing and externalizing factors (SMD=0.52 and SMD=0.36, respectively) than non-allergic children. Odds ratio (OR) analyses showed a higher risk (OR=2.76; 95% CI [1.61 to 4.72]) of developing a behavioural difficulty in children diagnosed with allergies. Age and level of asthma appear as modulatory variables.
Children aged 6–11 years diagnosed with allergies showed larger behavioural problems than non-allergic children. This relationship is stronger in internalizing behaviours. These findings suggest the importance of attending to them and treating them in the early stages of diagnosis to avoid future psychological disorders.
The Homa Peninsula has been known to science since 1911, and fossil specimens from the area comprise many type specimens for common African mammalian paleospecies. Here we discuss the fauna and the paleoenvironmental information from the Homa Peninsula. The Homa Peninsula is a 200 km2 area in Homa Bay County, situated on the southern margin of the Winam Gulf of Lake Victoria in Kenya (Figure 29.1). Lake Victoria is estimated to be the third largest lake in the world, with a surface area of 68,900 km2 and a maximum length of approximately 616 km. Although its catchment is extensive, it is relatively shallow compared to any other lake of similar size, with a maximum depth of 84 m. Lake Victoria is located in a depression formed by the western and eastern branches of the East African Rift System (EARS), and is at an average elevation of 1135 m a.s.l. (Database for Hydrological Time Series of Inland Waters, 2017).
The existence of a turbulent/turbulent interface (TTI) has recently been verified in the far wake of a circular cylinder exposed to free-stream turbulence (Kankanwadi & Buxton, J. Fluid Mech., vol. 905, 2020, p. A35). This study aims to understand the physics within the TTI. The wake boundary, approximately 40 diameters downstream of a circular cylinder subjected to grid-generated turbulence, was investigated through simultaneous cinematographic, stereoscopic particle image velocimetry and planar laser induced fluorescence experiments. With no grid placed upstream of the cylinder, the behaviour of the resultant interface, our closest approximation to a turbulent/non-turbulent interface, exactly matched what is observed in existing literature. When background turbulence is present, viscous action is no longer the only method by which enstrophy is transported to the background fluid, unlike for turbulent/non-turbulent interfaces. The presence of rotational fluid on both sides of the TTI allows the vorticity stretching term of the enstrophy budget equation to be the dominant actor in this process. The role of viscosity within a TTI is greatly diminished as the vorticity stretching term takes over responsibilities for enstrophy production. The turbulent strain rate normal to the TTI was found to be enhanced in the interfacial region. Decomposing the vorticity stretching term into components aligned with the three principal strain-rate directions, it was found that the term most aligned with the interface-normal direction contributed to the largest share of enstrophy production. This indicates that better ‘organised’ vorticity on the wake side of the interface yields the enstrophy amplification leading to the previously discovered enstrophy jump across the TTI by Kankanwadi & Buxton (J. Fluid Mech., vol. 905, 2020, p. A35).
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Mood disorders are characterised by pronounced symptom heterogeneity, which presents a substantial challenge both to clinical practice and research. Identification of subgroups of individuals with homogeneous symptom profiles that cut across current diagnostic categories could provide insights in to the transdiagnostic relevance of individual symptoms, which current categorical diagnostic systems cannot impart.
To identify groups of people with homogeneous clinical characteristics, using symptoms of manic and/or irritable mood, and explore differences between groups in diagnoses, functional outcomes and genetic liability.
We used latent class analysis on eight binary self-reported symptoms of manic and irritable mood in the UK Biobank and PROTECT studies, to investigate how individuals formed latent subgroups. We tested associations between the latent classes and diagnoses of psychiatric disorders, sociodemographic characteristics and polygenic risk scores.
Five latent classes were derived in UK Biobank (N = 42 183) and were replicated in the independent PROTECT cohort (N = 4445), including ‘minimally affected’, ‘inactive restless’, active restless’, ‘focused creative’ and ‘extensively affected’ individuals. These classes differed in disorder risk, polygenic risk score and functional outcomes. One class that experienced disruptive episodes of mostly irritable mood largely comprised cases of depression/anxiety, and a class of individuals with increased confidence/creativity reported comparatively lower disruptiveness and functional impairment.
Findings suggest that data-driven investigations of psychopathological symptoms that include sub-diagnostic threshold conditions can complement research of clinical diagnoses. Improved classification systems of psychopathology could investigate a weighted approach to symptoms, toward a more dimensional classification of mood disorders.
We analyzed the efficacy, cost, and cost-effectiveness of predictive decision-support systems based on surveillance interventions to reduce the spread of carbapenem-resistant Enterobacteriaceae (CRE).
We developed a computational model that included patient movement between acute-care hospitals (ACHs), long-term care facilities (LTCFs), and communities to simulate the transmission and epidemiology of CRE. A comparative cost-effectiveness analysis was conducted on several surveillance strategies to detect asymptomatic CRE colonization, which included screening in ICUs at select or all hospitals, a statewide registry, or a combination of hospital screening and a statewide registry.
We investigated 51 ACHs, 222 LTCFs, and skilled nursing facilities, and 464 ZIP codes in the state of Maryland.
Patients or participants:
The model was informed using 2013–2016 patient-mix data from the Maryland Health Services Cost Review Commission. This model included all patients that were admitted to an ACH.
On average, the implementation of a statewide CRE registry reduced annual CRE infections by 6.3% (18.8 cases). Policies of screening in select or all ICUs without a statewide registry had no significant impact on the incidence of CRE infections. Predictive algorithms, which identified any high-risk patient, reduced colonization incidence by an average of 1.2% (3.7 cases) without a registry and 7.0% (20.9 cases) with a registry. Implementation of the registry was estimated to save $572,000 statewide in averted infections per year.
Although hospital-level surveillance provided minimal reductions in CRE infections, regional coordination with a statewide registry of CRE patients reduced infections and was cost-effective.
We study the effects of fluid–particle and particle–particle interactions in a three-dimensional monodispersed reactor with unstable fluidization. Simulations were conducted using the immersed boundary method for particle Reynolds numbers of 20–70 with an Archimedes number of 23 600. Two different flow regimes were identified as a function of the particle Reynolds number. For low particle Reynolds numbers ($20 < Re_p < 40$), the porosity is relatively low and the particle dynamics are dominated by interparticle collisions that produce anisotropic particle velocity fluctuations. The relative importance of hydrodynamic effects increases with increasing particle Reynolds number, leading to a minimized anisotropy in the particle velocity fluctuations at an intermediate particle Reynolds number. For high particle Reynolds numbers ($Re_p > 40$), the particle dynamics are dominated by hydrodynamic effects, leading to decreasing and more anisotropic particle velocity fluctuations. A sharp increase in the anisotropy occurs when the particle Reynolds number increases from 40 to 50, corresponding to a transition from a regime in which collision and hydrodynamic effects are equally important (regime 1) to a hydrodynamic-dominated regime (regime 2). The results imply an optimum particle Reynolds number of roughly 40 for the investigated Archimedes number of 23 600 at which mixing in the reactor is expected to peak, which is consistent with reactor studies showing peak performance at a similar particle Reynolds number and with a similar Archimedes number. Results also show that maximum effective collisions are attained at intermediate particle Reynolds number. Future work is required to relate optimum particle Reynolds number to Archimedes number.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Designating protected areas remains a core strategy in biodiversity conservation. Despite high endemism, montane forests across the island of Java are under-represented in Indonesia's protected area network. Here, we document the montane biodiversity of Gunung Slamet, an isolated volcano in Central Java, and provide evidence to support its increased protection. During September–December 2018, we surveyed multiple sites for birds, primates, terrestrial mammals, reptiles, amphibians and vegetation. Survey methods included transects, camera traps and targeted searches at six sites, at altitudes of 970–2,512 m. We used species distribution models for birds and mammals of conservation concern to identify priority areas for protection. We recorded 99 bird species (13 globally threatened), 15 mammals (five globally threatened) and 17 reptiles and amphibians (two endemic). Our species distribution models showed considerable cross-taxon congruence between important areas on Slamet's upper slopes, generally above 1,800 m. Particularly important were records of the endemic subspecies of the Endangered Javan laughingthrush Garrulax rufifrons slamatensis, not recorded in the wild since 1925, the Endangered Javan gibbon Hylobates moloch and Javan surili Presbytis comata, and the Vulnerable Javan lutung Trachypithecus auratus and Javan leopard Panthera pardus melas. Recent forest loss has been modest, at least 280 km2 of continuous forest remain above 800 m, and our surveys show that forest habitats are in good condition. However, the mountain is widely used by trappers and hunters. Given its importance for biodiversity conservation, we discuss different options for improving the protection status of Gunung Slamet, including designation as a National Park or Essential Ecosystem.
We study the effects of Archimedes number $Ar$ and volume fraction $\phi$ in three-dimensional, high concentration and monodispersed particle suspensions. Simulations were conducted using the immersed boundary method with direct forcing for triply periodic cases and with $Ar = 21 - 23\,600$ and $\phi = 0.22 - 0.43$. We find that cluster formation is strongly dependent on the Archimedes number but weakly dependent on the volume fraction for concentrated suspensions. Particles in low $Ar$ cases are characterized by less frequent but long-lived clusters, resulting in higher hindered settling, while high $Ar$ cases consist of more frequent but short-lived clusters, leading to reduced hindered settling. By quantifying the effects of collisions on the hydrodynamic fluctuations, we show that the lifespan of clusters for the low $Ar$ cases is longer because particles are subject to appreciable wake interactions without collisions. On the other hand, clusters for high $Ar$ cases are broken before being subject to appreciable wake interactions due to frequent collisions, leading to a shorter cluster lifespan. The results imply that there exists an $Ar$ for particles in fluidized bed reactors that can reduce short circuiting due to clustering and enhance performance by maximizing flow–particle interactions. This result is consistent with existing reactor studies demonstrating that optimal particle diameters and $Ar$ values correspond to cases with short-lived clusters, although more thorough experimental studies are needed.
Anxiety and depression are leading causes of disability worldwide, yet individuals are often unable to access appropriate treatment. There is a need to develop effective interventions that can be delivered remotely. Previous research has suggested that emotional processing biases are a potential target for intervention, and these may be altered through brief training programs.
We report two experimental medicine studies of emotional bias training in two samples: individuals from the general population (n = 522) and individuals currently taking antidepressants to treat anxiety or depression (n = 212). Participants, recruited online, completed four sessions of EBT from their own home. Mental health and cognitive functioning outcomes were assessed at baseline, immediately post-training, and at 2-week follow-up.
In both studies, our intervention successfully trained participants to perceive ambiguous social information more positively. This persisted at a 2-week follow-up. There was no clear evidence that this change in emotional processing transferred to improvements in symptoms in the primary analyses. However, in both studies, there was weak evidence for improved quality of life following EBT amongst individuals with more depressive symptoms at baseline. No clear evidence of transfer effects was observed for self-reported daily stress, anhedonia or depressive symptoms. Exploratory analyses suggested that younger participants reported greater treatment gains.
These studies demonstrate the effectiveness of delivering a multi-session online training program to promote lasting cognitive changes. Given the inconsistent evidence for transfer effects, EBT requires further development before it can be considered as a treatment for anxiety and depression.